dwyer-antiinflammatoryand-2010.pdf (697.12 kB)
Antiinflammatory and anticoagulant effects of transgenic expression of human thrombomodulin in mice
journal contribution
posted on 2010-02-01, 00:00 authored by S Crikis, X M Zhang, S Dezfouli, Karen DwyerKaren Dwyer, L M Murray-Segal, E Salvaris, C Selan, S C Robson, H H Nandurkar, P J Cowan, A J F d'ApiceThrombomodulin (TBM) is an important vascular anticoagulant that has species specific effects. When expressed as a transgene in pigs, human (h)TBM might abrogate thrombotic manifestations of acute vascular rejection (AVR) that occur when GalT-KO and/or complement regulator transgenic pig organs are transplanted to primates. hTBM transgenic mice were generated and characterized to determine whether this approach might show benefit without the development of deleterious hemorrhagic phenotypes. hTBM mice are viable and are not subject to spontaneous hemorrhage, although they have a prolonged bleeding time. They are resistant to intravenous collagen-induced pulmonary thromboembolism, stasis-induced venous thrombosis and pulmonary embolism. Cardiac grafts from hTBM mice to rats treated with cyclosporine in a model of AVR have prolonged survival compared to controls. hTBM reduced the inflammatory reaction in the vein wall in the stasis-induced thrombosis and mouse-to-rat xenograft models and reduced HMGB1 levels in LPS-treated mice. These results indicate that transgenic expression of hTBM has anticoagulant and antiinflammatory effects that are graft-protective in murine models.
History
Journal
American journal of transplantationVolume
10Issue
2Pagination
242 - 250Publisher
John Wiley & SonsLocation
Chichester, Eng.Publisher DOI
eISSN
1600-6143Language
engPublication classification
C1.1 Refereed article in a scholarly journalCopyright notice
2010, The AuthorsUsage metrics
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No categories selectedKeywords
AnimalsAnti-Inflammatory AgentsCyclosporineDisease Models, AnimalHumansMiceMice, TransgenicRatsSwineThrombomodulinTransgenesAcuteclotting factorscoagulationcoagulation factorsrejectionthrombosistransgenicvascularxenotransplantationScience & TechnologyLife Sciences & BiomedicineSurgeryTransplantationTHROMBIN-INDUCED THROMBOEMBOLISMRECOMBINANT HUMAN ANTITHROMBINPROTEIN-C RECEPTORXENOGRAFT REJECTIONRHS-TMPIGENDOTHELIUMMOUSE
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